Higher Respiration Rates Research Articles

5-ALA Is a Potent Lactate Dehydrogenase Inhibitor but Not a Substrate: Implications for Cell Glycolysis and New Avenues in 5-ALA-Mediated Anticancer Action.

Simple SummaryIn the present work, we found that 5-ALA, a natural precursor of heme, can hinder cell glycolysis, which is the main path of energy production for most cancer cells. More specifically, we found that 5-ALA can block an enzyme involved in glycolysis, called lactate dehydrogenase (LDH). We found that 5-ALA has a potency of LDH inhibition comparable to other established LDH inhibitors, such as oxamate or tartronic acid. Nevertheless, 5-ALA has a high accumulation rate in cancers and specifically in the incurable brain cancer glioblastoma multiforme (GBM), which is an important advantage. In fact, because of its high specificity to GBM, 5-ALA is used in the clinic to accurately guide the resection of the tumours, through the light emission of its photoactive product protoporphyrin IX (PpIX). PpIX is the penultimate step in the heme production. Importantly, we show here that continuous administration of 5-ALA killed GBM cells according to their dependence on glycolysis. We additionally found that 20% of externally administered 5-ALA is engaged in the inhibition of LDH, as when LDH was pre-loaded by another inhibitor, tartronic acid, then the cell production of PpIX from 5-ALA was increased by 20%. Since PpIX is an important drug for photodynamic therapy of cancer (excitation by light of PpIX produces oxygen by-products that can kill cancer cells), we additionally discovered that preloading LDH with its inhibitor tartronic acid before performing 5-ALA PDT increases the cancer cell death by 15%.In a course of metabolic experiments, we determined that the addition of δ-aminolevulinic acid (5-ALA) to a panel of glioblastoma multiforme (GBM) cells caused a steep reduction in their glycolytic activity. This reduction was accompanied by a decrease in adenosine triphosphate (ATP) production from glycolysis. These results suggested that 5-ALA is an inhibitor of glycolysis; due to the structural similarity of 5-ALA to the established lactate dehydrogenase (LDH) inhibitors oxamate (OXM) and tartronate (TART), we initially investigated LDH inhibition by 5-ALA in silico. The modelling revealed that 5-ALA could indeed be a competitive inhibitor of LDH but not a substrate. These theoretical findings were corroborated by enzymatic and cell lysate assays in which 5-ALA was found to confer a potent LDH inhibition comparable to that of OXM and TART. We subsequently evaluated the effect of 5-ALA-induced glycolysis inhibition on the viability of GBM cells with diverse metabolic phenotypes. In the Warburg-type cell lines Ln18 and U87, incubation with 5-ALA elicited profound and irreversible cell death (90–98%) at 10 mM after merely 24 h. In T98G, however, which exhibited both high respiratory and glycolytic rates, LD95 was achieved after 72 h of incubation with 20 mM 5-ALA. We additionally examined the production of the 5-ALA photosensitive metadrug protoporphyrin IX (PpIX), with and without prior LDH inhibition by TART. These studies revealed that ~20% of the 5-ALA taken up by the cells was engaged in LDH inhibition. We subsequently performed 5-ALA photodynamic therapy (PDT) on Ln18 GBM cells, again with and without prior LDH inhibition with TART, and found a PDT outcome enhancement of ~15% upon LDH pre-inhibition. We expect our findings to have a profound impact on contemporary oncology, particularly for the treatment of otherwise incurable brain cancers such as GBM, where the specific accumulation of 5-ALA is very high compared to the surrounding normal tissue.

Initial emergency department vital signs may predict PICU admission in pediatric patients presenting with asthma exacerbation

Objective Severe asthma exacerbations account for a large share of asthma morbidity, mortality, and costs. Here, we aim to identify early predictive factors associated with pediatric intensive care unit (PICU) admission. Methods We performed a retrospective observational study of 5,185 emergency department (ED) encounters at a large children’s hospital, including 86 (1.7%) resulting in PICU admission between 10/1/2015 and 8/7/2018 with ICD9/ICD10 codes for “asthma,” “bronchospasm,” or “wheezing.” Vital signs and demographic information were obtained from electronic health record data and analyzed for each encounter. Predictive factors were identified using adjusted regression models, and our primary outcome was PICU admission. Results Higher mean heart rates (HRs) and respiratory rates (RRs), and lower SpO2 within the first hour of ED presentation were independently associated with PICU admission. Odds of PICU admission increased 70% for each 10 beats/min higher HR, 125% for each 10 breaths/min higher RR, and 34% for each 5% lower SpO2. A binary predictive index using 1-h vitals yielded OR 13.4 (95% CI 8.1–22.1) for PICU admission, area under receiver operator characteristic (AUROC) curve 0.84 and overall accuracy of 80.1%. Results were largely unchanged (AUROC 0.84–0.88) after adjusting for surrogates of asthma severity and initial ED management. In combination with a secondary standardized clinical asthma distress score, positive predictive value increased by sevenfold (6.1%–46%). Conclusions A predictive index using HR, RR, and SpO2 within the first hour of ED presentation accurately predicted PICU admission in this cohort. Automated vital signs trend analysis may help identify vulnerable patients quickly upon presentation.

Toxicity Assessment of an Anti-Cancer Drug of p-Toluene Sulfonamide in Zebrafish Larvae Based on Cardiovascular and Locomotion Activities.

p-Toluene sulfonamide (p-TSA), a small molecular drug with antineoplastic activity is widely gaining interest from researchers because of its pharmacological activities. In this study, we explored the potential cardio and neural toxicity of p-TSA in sublethal concentrations by using zebrafish as an in vivo animal model. Based on the acute toxicity assay, the 96hr LC50 was estimated as 204.3 ppm, suggesting the overall toxicity of p-TSA is relatively low in zebrafish larvae. For the cardiotoxicity test, we found that p-TSA caused only a minor alteration in treated larvae after no overall significant alterations were observed in cardiac rhythm and cardiac physiology parameters, as supported by the results from expression level measurements of several cardiac development marker genes. On the other hand, we found that acute p-TSA exposure significantly increased the larval locomotion activity during the photomotor test while prolonged exposure (4 days) reduced the locomotor startle reflex activities in zebrafish. In addition, a higher respiratory rate and blood flow velocity was also observed in the acutely treated fish groups compared to the untreated group. Finally, by molecular docking, we found that p-TSA has a moderate binding affinity to skeletal muscle myosin II subfragment 1 (S1), ATPase activity, actin- and Ca2+-stimulated myosin S1 ATPase, and v-type proton ATPase. These binding interactions between p-TSA and proteins offer insights into the potential molecular mechanism of action of p-TSA on observed altered responses toward photo and vibration stimuli and minor altered vascular performance in the zebrafish larvae.

Immobilization of Captive Kulans (Equus hemionus kulan) Without Using Ultrapotent Opioids.

Etorphine is widely used in zoological medicine for the immobilization of large herbivores. All reported immobilization protocols for kulans use etorphine as the primary immobilizing agent. However, etorphine can trigger severe side effects and is highly toxic for humans, its availability is occasionally limited for use in wildlife medicine. Therefore, two different alpha-2 agonist-based protocols for the general anesthesia of kulans were investigated and compared with the standard etorphine immobilization. In total, 21 immobilizations were performed within the scope of routine husbandry management at the Serengeti-Park Hodenhagen. Kulans were darted using a ketamine–medetomidine–midazolam–butorphanol (KMMB) protocol (n = 8, treatment group (TG) 1), a tiletamine–zolazepam–medetomidine–butorphanol (TZMB) protocol (n = 7, treatment group (TG) 2), or an etorphine–acepromazine–detomidine–butorphanol (EADB) protocol (n = 6, control group). Vital parameters included heart rate, respiratory rate, arterial blood pressure (invasive), end tidal CO2 (etCO2), electromyography and core body temperature, which were all assessed every 10 min. For blood gas analysis, arterial samples were collected 15, 30, 45 and 60 min after induction. Subjective measures of quality and efficacy included quality of induction, immobilization, and recovery. Time to recumbency was longer for TG 1 (9.00 ± 1.67 min) and TG 2 (10.43 ± 1.79 min) compared to the induction times in the control group (5.33 ± 1.93 min). Treatment group protocols resulted in excellent muscle relaxation, normoxemia and normocapnia. Lower pulse rates combined with systolic arterial hypertension were detected in the alpha-2 agonist-based protocols. However, only in TZMB-immobilized kulans, sustained severe systolic arterial hypertension was observed, with significantly higher values than in the TG 1 and the normotensive control group. At 60 min following induction, medetomidine and detomidine were antagonized with atipamezole IM (5 mg/mg medetomidine or 2 mg/mg detomidine), etorphine and butorphanol with naltrexone IV (2 mg/mg butorphanol or 50 mg/mg etorphine), and midazolam and zolazepam with flumazenil IV (0.3 mg per animal). All three combinations provided smooth and rapid recoveries. To conclude, the investigated treatment protocols (KMMB and TZMB) provided a safe and efficient general anesthesia in kulans with significantly better muscle relaxation, higher respiration rates and improved arterial oxygenation compared with the immobilizations of the control group. However, the control group (EADB) showed faster recoveries. Therefore, EADB is recommended for ultra-short immobilizations (e.g., microchipping and collaring), especially with free-ranging kulans where individual recovery is uncertain, whereas the investigated treatment protocols are recommended for prolonged medical procedures on captive kulans.

A Machine Learning Model for Predicting Hospitalization in Patients with Respiratory Symptoms during the COVID-19 Pandemic.

A machine learning approach is a useful tool for risk-stratifying patients with respiratory symptoms during the COVID-19 pandemic, as it is still evolving. We aimed to verify the predictive capacity of a gradient boosting decision trees (XGboost) algorithm to select the most important predictors including clinical and demographic parameters in patients who sought medical support due to respiratory signs and symptoms (RAPID RISK COVID-19). A total of 7336 patients were enrolled in the study, including 6596 patients that did not require hospitalization and 740 that required hospitalization. We identified that patients with respiratory signs and symptoms, in particular, lower oxyhemoglobin saturation by pulse oximetry (SpO2) and higher respiratory rate, fever, higher heart rate, and lower levels of blood pressure, associated with age, male sex, and the underlying conditions of diabetes mellitus and hypertension, required hospitalization more often. The predictive model yielded a ROC curve with an area under the curve (AUC) of 0.9181 (95% CI, 0.9001 to 0.9361). In conclusion, our model had a high discriminatory value which enabled the identification of a clinical and demographic profile predictive, preventive, and personalized of COVID-19 severity symptoms.

Zonations and oscillations via heterotrophic processes in tidal unvegetated aquifers

AbstractGlobal‐change drivers that alter tidal amplitude or sea level could directly impact coastal aquifers' seawater–microbe interactions. The semidiurnal or diurnal tide can have consequences for chemical redistribution, because it deepens oxygen and nutrients penetration depth, thereby increasing O2 depletion via microbial respiration in sediments during groundwater circulation. However, chemical and microbial distributions in tidal aquifers remain unclear, in deference to their link with depth and lateral location. By combining the microbes‐accumulated equation with the traditional groundwater flow model in coastal aquifers, we explicitly unravelled the heterotrophic zonation, the salinity zonation, and the oxic zonation of tidal aquifers. According to the model estimates, salt penetrates deeper than reactive chemicals, and the heterotrophic high biomass zone is presumably 2–3 m deep. Such depth of heterotrophic distribution is 2–3 orders of magnitude higher than phototrophic distribution. Additionally, heterotrophic biomass can exhibit faint oscillations, even under the tide forces, whereas dissolved chemicals fluctuate significantly with tidal pumps. Due to the transport of nutrients by tidal penetration, intertidal sediments have a higher respiration rate than subtidal sediments, converting more organic carbon from seawater to atmospheric CO2 via microbes. We demonstrate that heterotrophic biomass may play the dominant role in the chemical reactions of nearshore sediments. Our results confirm the efficacy of unvegetated tidal sediments that rely on ubiquitous heterotrophs as a driver of oxygen consumption and DOC transformation. These steps above will allow for better field investigations of coastal aquifers within a framework of zonations and oscillations.

Predicting the Risk of in-Hospital Mortality in Patients with HIV-Associated Talaromyces Marneffei Infection

Disseminated Talaromyces marneffei infection (formerly termed penicilliosis) is the third most common microbiologically confirmed opportunistic infection in Southeast Asia, with mortality of up to 30% despite antifungal therapy. There are restrictive clinical algorithms to predict treatment outcomes. A total of 513 patients with microbiology-confirmed HIV-associated talaromycosis were included in the analysis. Poor outcome was observed in 143/513 patients (27.9%). In the univariate logistic regression analysis, hepatomegaly and splenomegaly were protective factors. Shorter duration of illness, higher respiratory rates, dyspnea, AIDS-associated central nervous system syndromes, platelet counts <50,000 cells/mL, aspartate transaminase (AST) >300 U/L, alanine transaminase (ALT) >150 U/L, serum creatinine >110 µmol/L were predictors of poor outcome. In the multivariate logistic regression analysis, shorter days of illness, higher respiratory rates, platelet counts <50,000 cells/mL, AST >300 U/L and serum creatinine >110 µmol/L, active tuberculosis (TB) and/or ongoing TB induction treatment and AIDS-associated central nervous system syndromes were independent predictors of poor outcome. The prognostic scores ranged from 0 to 19, corresponding to a mortality risk of 0% to 100%. The internal validation showed acceptable discrimination (AUC=0.68) and calibration slope (0.93). The Brier score for model performance was 0.14. We developed a simple scoring system that can predict the risk of death in patients with HIV-associated talaromycosis based on routinely measured characteristics on admission. The scoring system will be further externally validated using other cohorts in the region.

Determination of the relationship between respiration rate and ethylene production by fruit sizes of different tomato types.

Tomatoes of different types and cultivars are grown in different parts of the world. Accordingly, the phenological, pomological and biochemical characteristics of these types and cultivars may differ from each other, and therefore their ripening behaviours may also differ. The present study aimed to determine the respiration rate and ethylene production of twelve commonly grown cultivars in Turkey at harvest and during the ripening stage. The fruits were harvested at the mature green stage and categorized according to their size as small, medium and large-fruited cultivars. At harvest time, the highest respiration rate was determined from 'Moda' (small-fruited) cultivar and the lowest was from 'Elips' (medium-fruited). The highest ethylene production was determined from 'Sarikiz' (small-fruited) and the lowest was from 'Alberty' (large-fruited). All tomato cultivars examined in the study showed climacteric respiration behavior during the ripening, and it was determined that small-fruited types had a higher respiration rate and ethylene production compared to medium and large-fruited ones. 'Sarikiz' (small-fruited) had the highest climacteric peak and 'Gulpembe' (large-fruited) had the lowest. Moreover, it was determined that the respiration rate of small-fruited cultivars were 5.01-fold higher compared to other cultivars and this type of cultivars produced 4.19-fold higher ethylene compared to big-fruited cultivars at harvest. Medium-fruited tomatoes had 1.90-fold higher respiration rate and 1.64-fold ethylene production compared to big-fruited tomatoes. It was determined that fruit size and respiration rate were related independently of the cultivars, although there was no relationship between fruit size and ethylene production. © 2022 Society of Chemical Industry.

Effect of polysaccharide based edible coating to improve shelf ­life and quality of guava (Psidium guajava) in Malwa region of central India

Guava fruit have a very short shelf life due to high rate of respiration. Storage of guava fruits at room temperature causes weight loss, microbial disease, physiological disorders and physical injuries and is moreover, highly susceptibility to chilling injury making low temperature storage less possible. Therefore, the present investigation was carried out at the Department of Fruit Science, College of Horticulture, Mandsaur, Madhya Pradesh, India during the year 2019- 2020 with an objective to extend shelf-life of guava fruits cv. Rewa-72. The treatments comprised of post-harvest treatments with Chitosan, Carboxymethyl cellulose, Aloe vera gel. The physico-chemical, functional and sensory quality of guava fruits were significantly influenced by application Chitosan @ 1.5% and Carboxymethyl cellulose @ 1.5%) coating up to 12 days of storage. It was found that the CMC or Chitosan bilayer coating was equally effective as the commercial polyethylene wax in enhancing glossy appearance of guava fruits because it is a good moisture barrier, thus preventing the water loss by transpiration. Chitosan @ 1.5% and CMC @1.5% treated fruits had more overall acceptability because this coating helped in improving the colour, aroma, taste, texture, appearance and quality of fruits. Hence, this technology could be more useful for increase shelf life of fruits, low cost and reduce the post-harvest loss of fruits it also helps to replace the use of harmful chemicals by growers and traders.

Comparative Effects of Microalgal Species on Growth, Feeding, and Metabolism of Pearl Oysters, Pinctada fucata martensii and Pinctada maxima

Pinctada fucata martensii and P. maxima are two main traditional pearl oyster species that can produce seawater pearls. Our previous study showed a higher clearance rate (CR) and growth performance in P. f. martensii than in P. maxima fed with Isochrysis galbana. In this study, the P. f. martensii and P. maxima juveniles of two sizes (large and small) were fed with six different microalgae diets [I. galbana (I), Platymonas subcordiformis (P), Chaetoceros muelleri I, I+P, I+C, and P+C] to evaluate the differences in growth, feeding, and metabolism between two pearl oyster species. After 60 d of the rearing period, P. f. martensii and P. maxima fed with mixed microalgae showed a significantly higher relative growth rate (RGR) than those fed with single microalgae (P< 0.05). The RGRs were significantly higher in P. f. martensii than those in P. maxima fed with the same diets (P< 0.05). The RGRs showed a decreasing tendency with the growth in both pearl oyster species. The CRs of pearl oysters fed with mixed microalgae were significantly higher than those fed with single microalgae (P< 0.05), and the CRs of P. f. martensii were significantly higher than those of P. maxima fed with the same diets (P< 0.05). Significantly lower respiration rates (RRs) were observed in small-size P. f. martensii groups fed with I, P, and I+P diets and all large P. f. martensii groups compared to P. maxima fed with the same diets (P< 0.05). Higher activities of amylase, cellulase, lipase, and pepsin in P. f. martensiiwere observed compared to P. maxima fed with the same diets at two sizes. The pepsin activities in P. maxima decreased with the growth, while there were no consistent pepsin activities of P. f. martensii with the growth. The carbonic anhydrase activities in P. maxima were significantly higher than those in P. f. martensii fed with the same diets (P< 0.05). The carbonic anhydrase activities were highest in the I+C diet group, followed by C+P and I+P, I, C, and P groups. Significant differences were observed among different diet groups in the same pearl oyster species (P< 0.05). Our results suggest that the lower CR and activities of digestive enzymes and higher RRs and activities of carbonic anhydrase may cause a lower growth rate of P. maxima compared to P. f. martensii.

Partitioning inorganic carbon fluxes from paired O2–CO2 gas measurements in a Neotropical headwater stream, Costa Rica

The role of streams and rivers in the global carbon (C) cycle remains unconstrained, especially in headwater streams where CO2 evasion (FCO2) to the atmosphere is high. Stream C cycling is understudied in the tropics compared to temperate streams, and tropical streams may have among the highest FCO2 due to higher temperatures, continuous organic matter inputs, and high respiration rates both in-stream and in surrounding soils. In this paper, we present paired in-stream O2 and CO2 sensor data from a headwater stream in a lowland rainforest in Costa Rica to explore temporal variability in gas concentrations and ecosystem processes. Further, we estimate groundwater CO2 inputs (GWCO2) from riparian well CO2 measurements. Paired O2–CO2 data reveal stream CO2 supersaturation driven by groundwater CO2 inputs and large in-stream production of CO2. At short time scales, CO2 was diluted during storm events, but increased at longer seasonal scales. Areal fluxes in our study reach show that FCO2 is supported by greater in-stream metabolism compared to GWCO2. Our results underscore the importance of tropical headwater streams as large contributors of carbon dioxide to the atmosphere and show evaded C can be derived from both in-stream and terrestrial sources.

Clinical feasibility of an advanced neonatal epidermal multiparameter continuous monitoring technology in a large public maternity hospital in Nairobi, Kenya

Clinically feasible multiparameter continuous physiological monitoring technologies are needed for use in resource-constrained African healthcare facilities to allow for early detection of critical events and timely intervention for major morbidities in high-risk neonates. We conducted a prospective clinical feasibility study of a novel multiparameter continuous physiological monitoring technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of Sibel’s Advanced Neonatal Epidermal (ANNE) technology to reference technologies, including Masimo’s Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) measurements and Spengler’s Tempo Easy non-contact infrared thermometer for temperature measurements. We evaluated key performance criteria such as up-time, clinical event detection performance, and the agreement of measurements compared to those from the reference technologies in an uncontrolled, real-world setting. Between September 15 and December 15, 2020, we collected and analyzed 503 h of ANNE data from 109 enrolled neonates. ANNE’s up-time was 42 (11%) h more for HR, 77 (25%) h more for RR, and 6 (2%) h less for SpO2 compared to the Rad-97. However, ANNE’s ratio of up-time to total attached time was less than Rad-97’s for HR (0.79 vs 0.86), RR (0.68 vs. 0.79), and SpO2 (0.69 vs 0.86). ANNE demonstrated adequate performance in identifying high and low HR and RR and high temperature events; however, showed relatively poor performance for low SpO2 events. The normalized spread of limits of agreement were 8.4% for HR and 52.2% for RR and the normalized root-mean-square deviation was 4.4% for SpO2. Temperature agreement showed a spread of limits of agreement of 2.8 °C. The a priori-identified optimal limits were met for HR and temperature but not for RR or SpO2. ANNE was clinically feasible for HR and temperature but not RR and SpO2 as demonstrated by the technology’s up-time, clinical event detection performance, and the agreement of measurements compared to those from the reference technologies.

Postharvest High-CO2 Treatments on the Quality of Soft Fruit Berries: An Integrated Transcriptomic, Proteomic, and Metabolomic Approach.

Soft fruits are appreciated for their taste qualities and for being a source of health-promoting compounds. However, their postharvest is affected by their high respiratory rates and susceptibility to fungal decay. Our aim here is to provide a perspective on the application of short-term high-CO2 treatments at a low temperature to maintain the postharvest quality of soft fruits. This work also suggests using a multi-omics approach to better understand the role of the cell wall and phenolic compounds in maintaining quality. Finally, the contribution of high-throughput transcriptomic technologies to understand the mechanisms modulated by the short-term gaseous treatments is also highlighted.

The protective role of wallowing against heat stress in gestating and lactating sows housed outdoors

The objective of this study was to describe the physiological response of gestating and lactating sows to naturally-occurring environmental conditions, and to identify factors that may contribute to or prevent heat stress, while being kept outdoors in Québec, Canada during the summer. Six groups of 4 Yorkshire-Landrace sows lived in outdoor pens equipped with a wallow, shade structure, farrowing huts and access to a pasture from July to September 2018. Between week 15 of gestation and week 3 of lactation (inclusive), we recorded the location of each sow 5 days/week during 5 daily 15-min observation periods, and additionally measured the sow's respiratory rate and mud cover at the end of each observation period. Simultaneously, we collected sow body temperature data with vaginal temperature loggers 24 h/d on week 15 of gestation and week 2 of lactation, and monitored environmental conditions with temperature and humidity loggers to calculate the temperature humidity index (THI). Sows had significantly higher and more variable body temperatures during lactation compared to gestation (P ≤ 0.0001), and when THI was analysed as a continuous variable, it was positively associated with sow body temperature during the night in lactation. During gestation, neither respiratory rate nor body temperature were associated with high or low levels of THI (P = 0.15 and 0.79, respectively) or mud cover (P = 0.29 and 0.94, respectively). However, in lactation, respiratory rate was higher when, simultaneously, THI exceeded 74 and mud cover was low (P = 0.006), while a THI higher than 74 and a low mud cover had independent effects on body temperature (P = 0.012 and 0.004, respectively). In lactation, sows that spent an entire observation period in the farrowing hut also had a higher respiratory rate than sows that left the hut at least once (P = 0.009). In summary, lactating sows were more likely to show increases in respiratory rate and body temperature in warmer conditions than gestating sows, and our findings also suggest that time in the farrowing hut may be a risk factor for heat stress. However, mud cover may limit these physiological consequences when sows have access to a wallow.

Synchronised interaction of carbon and nitrogen provides drought tolerance in Cyamopsis tetragonoloba

Drought is a major adverse environmental factor that limits plant productivity. Concomitant assimilation of carbon (C) and nitrogen (N) in illuminated leaves requires the regulated partitioning of reductant and photosynthate to sustain the demands of amino acid and carbohydrate biosynthesis. The short-term exposure to drought and its responses of photosynthesis and photosynthate partitioning to N enrichment was studied in Cyamopsis tetragonoloba (L.) Taub (guar). Four contrasting varieties of guar, HG-563, RGC-986 (drought-tolerant) and RGC-471, Varsha (drought-sensitive) were subjected to 15 days water stress and leaf tissues were studied in order to contemplate the counter strategy engaged under drought conditions. In guar plants, sensors trigger a signalling cascade that activates numerous proteins to induce the expression of certain genes involved in carbon and nitrogen metabolism.The levels of glucose, starch, and Glutamate dehydrogenase (GDH), Aspartate aminotransferase (AspAT), isocitrate dehydrogenase (ICDH), Nitrate Reductase (NR), and Nitrite reductase (NiR) activities were determined biochemically during 15 days drought treatment, at three stages. Further, the carbon (oxidative phosphorylation and TCA cycle) - nitrogen metabolic pathway interaction was studied at the molecular level. The respiratory pathway genes were upregulated, while the nitrogen metabolic pathway genes were downregulated under all stages of drought in guar plants. The physiological, biochemical and molecular data suggests that the high rates of dark respiration was insufficient to provide extra carbon required to assist amino acid synthesis but rather sufficed by a rapid metamorphosis in the photosynthetic carbon partitioning to amino acid metabolism via the nitrogen metabolism. • Drought causes NADH DEHYDROGENASE gene to escalate dark respiration. • Nitrogen assimilation reduces under drought in leguminous Cyamopsis tetragonoloba. • Drought triggers protein kinase cascade signalling in guar plants. • Drought regulates nitrogen metabolic genes in guar. • Drought triggers increase in sugar content at the cost of amino acids.

Soursop fruit storage: Edible coating based on Hibiscus sabdariffa mucilage

Soursop fruit (Annona muricata L.) is a crop of important economic value for the state of Nayarit, however, it has a fast ripening that causes a short shelf life. Several post-harvest handling techniques have been applied to reduce its metabolic processes, such as refrigeration, the use of 1-methylcyclopropene (1-MCP) and controlled and modified atmospheres. In recent years, polysaccharide-based coatings have been applied to fruits. The aim of this research was to evaluate the physicochemical changes of soursop fruits coated with hibiscus calyx mucilage (2%), stored at 22 °C and 15 °C. Weight loss, firmness, pH, total soluble solids, acidity and colour were evaluated. Results for coated fruits stored at 15 °C showed lower weight loss (6.4%), lower firmness (29.7 N), higher TSS concentration (10.4 °Bx) and lower acidity (0.38%) compared to uncoated fruits. Coating with hibiscus mucilage and storage at 15 °C for four days decreased fruit weight loss. It was also observed that storage under these conditions allows a lower concentration of total soluble solids and organic acids. The coatings did not intervene in the decrease of fruit peel colour. Key words: coating, mucilage, soursop, postharvest. Introduction Mexico is the world's leading producer of soursop, with a national production of 30, 790 T in 2019. In this sense, the state of Nayarit was the largest producer of soursop with 23,230 T (Servicio de Información Agroalimentaria y Pesquera [SIAP], 2020). Soursop production contributes to the economic growth of Nayarit; however, there is a problem in the handling of the fruit due to the high respiration rate and ethylene production leading to softening of the fruit, resulting in a short post-harvest shelf life (Balois-Morales et al., 2019). Nayarit does not have an adequate postharvest system, which leads to inadequate fruit handling during handling (Jiménez-Zurita et al., 2016), causing production losses (Tovar-Gómez et al., 2011). Therefore, there is interest in investigating postharvest technologies that allow prolonging shelf life while maintaining the nutritional quality of the fruit (Moreno-Hernández et al., 2014). As an alternative to improve postharvest handling and maintain the quality of fruit and vegetable products, the use of edible coatings has been implemented (Park et al., 2014). Edible coatings based on polysaccharides have gained importance because they create a modified atmosphere through a semi-permeable layer in the fruit that allows gas exchange, reducing metabolic processes and prolonging the postharvest life of the fruit (Solano-Doblado et al., 2018). Among the polysaccharides of interest, mucilages have been used due to their highly branched structure, complex polymeric and hydrocarbon nature that allows modifying the rheology of a solution (Dugarte et al., 2019). Coatings made from mucilage allow a decrease in weight loss, delay in the concentration of total soluble solids, as well as colour improvement (Zambrano et al., 2017). In the above context, hibiscus mucilage could be used as a material for the preparation of an edible coating to prolong the shelf life of fruits. With this in mind, the effect of hibiscus mucilage-based coating (2%) on physicochemical changes during postharvest storage was evaluated in this study.

Synergistic Effect of Calcium Chloride and Chitosan Treatment on Physicochemical Characteristics of Pineapple (Ananas Comosus) Fruit During Cool Storage

Pineapple (Ananascomosus) is one of the most popular agricultural products in the world. It is well-known for its excellent flavour and taste, diversified valuable nutritional components as well as phytochemical and antioxidant properties. However it is quite perishable at ambient condition due to its high respiration rate. It is essential to find an appropriate strategy to extend its stability during storage. This study concentrates on the effectiveness of calcium chloride and chitosan treatments on the post-harvest physicochemical quality of pineapple during storage at 12oC and 80±5% relative humidity. The fruit was treated with different concentrations of CaCl2 (0.5%, 1.0%, 1.5%, 2.0%, 2.5%) via dipping for 4 min and chitosan (0.5%, 1.0%, 1.5%, 2.0%, 2.5% w/v) via coating. Different physicochemical parameters such as weight loss (%), firmness (N), decay percentage (%), total soluble solid (oBrix), ascorbic acid (mg/100g) were thoroughly examined, Our results showed that a combination of 2.0% CaCl2 with 1.5% chitosan created a synergistic effect on physicochemical characteristics of pineapple fruit during 14 days of cool storage. These results implied that calcium chloride combined with chitosan as edible coatings have potential to maintain fruit quality in respect of weight loss, firmness, total soluble solid, ascorbic acid while reducing post harvest spoilage (decay) in pineapple fruit.

Deciding When to Intubate a COVID-19 Patient.

The SARS-CoV-2 pandemic is one of the most significant challenges for healthcare providers, particularly in the critical care setting. The timing of intubation in COVID-19 patients seems to be challenging. Therefore, we aimed to investigate how it may have a survival benefit, and we determined which clinical characteristics were associated with outcomes. This cross-sectional study was conducted in the Imam Khomeini Hospital Complex. We randomly selected patients admitted to intensive care units and, based on intubation status, categorized them into three subgroups (early, late, and not intubated). Early intubation is defined as intubation within 48 hours of ICU admission, and late intubation is defined as intubation after 48 hours of ICU admission. Early-intubated patients were more likely to have dyspnea than late-intubated patients, and late-intubated patients had a higher mean heart rate than early-intubated patients. The neutrophil/lymphocyte ratio was significantly (P < 0.05) lower in not-intubated patients than in other patients. There was no difference in NLR between early- and late-intubated patients. Mean serum creatine phosphokinase and troponin I levels were higher in late-intubated patients than in early- and not-intubated patients. Early-intubated patients had a lower ROX index than late-intubated patients. Patients with higher scores of APACHE 2, respiratory rates, and neutrophil to lymphocyte ratio were more likely to be intubated. Increasing APACHE and SOFA scores were associated with decreased odds of survival. There were no statistically significant differences in total mortality between early- and late-intubated patients. APACHE 2 scores, NLR, RR, and history of ischemic heart disease are some of the appropriate predictors of intubation. Higher respiratory rates (tachypnea) can be an indicator of early intubation. The ROX index is one of the most sensitive and capable tools for predicting intubation. Intubation status is a potent predictor of in-hospital mortality.

Cardiovascular Risk Factors and Clinical Outcomes among Patients Hospitalized with COVID-19: Findings from the World Heart Federation COVID-19 Study.

Background and aims:Limited data exist on the cardiovascular manifestations and risk factors in people hospitalized with COVID-19 from low- and middle-income countries. This study aims to describe cardiovascular risk factors, clinical manifestations, and outcomes among patients hospitalized with COVID-19 in low, lower-middle, upper-middle- and high-income countries (LIC, LMIC, UMIC, HIC).Methods:Through a prospective cohort study, data on demographics and pre-existing conditions at hospital admission, clinical outcomes at hospital discharge (death, major adverse cardiovascular events (MACE), renal failure, neurological events, and pulmonary outcomes), 30-day vital status, and re-hospitalization were collected. Descriptive analyses and multivariable log-binomial regression models, adjusted for age, sex, ethnicity/income groups, and clinical characteristics, were performed.Results:Forty hospitals from 23 countries recruited 5,313 patients with COVID-19 (LIC = 7.1%, LMIC = 47.5%, UMIC = 19.6%, HIC = 25.7%). Mean age was 57.0 (±16.1) years, male 59.4%, pre-existing conditions included: hypertension 47.3%, diabetes 32.0%, coronary heart disease 10.9%, and heart failure 5.5%. The most frequently reported cardiovascular discharge diagnoses were cardiac arrest (5.5%), acute heart failure (3.8%), and myocardial infarction (1.6%). The rate of in-hospital deaths was 12.9% (N = 683), and post-discharge 30 days deaths was 2.6% (N = 118) (overall death rate 15.1%). The most common causes of death were respiratory failure (39.3%) and sudden cardiac death (20.0%). The predictors of overall mortality included older age (≥60 years), male sex, pre-existing coronary heart disease, renal disease, diabetes, ICU admission, oxygen therapy, and higher respiratory rates (p < 0.001 for each). Compared to Caucasians, Asians, Blacks, and Hispanics had almost 2–4 times higher risk of death. Further, patients from LIC, LMIC, UMIC versus. HIC had 2–3 times increased risk of death.Conclusions:The LIC, LMIC, and UMIC’s have sparse data on COVID-19. We provide robust evidence on COVID-19 outcomes in these countries. This study can help guide future health care planning for the pandemic globally.

Abstract 3773: Mitochondrial fusion is required to support higher rates of respiration in proliferating cancer cells

Abstract Proliferating cancer cells exhibit an elevated rate of glucose consumption and lactate excretion, a phenomenon described as the “Warburg effect”. Although increased glycolytic flux in proliferating cells is well established, metabolic changes associated with mitochondria still remain elusive. Here, using various inducible quiescence models and mass spectrometry-based metabolomics, we directly compared mitochondrial respiration and TCA cycle activity from the same cells in the proliferative and quiescent states. We found that mitochondrial respiration and TCA cycle flux is significantly increased during proliferation in both transformed and non-transformed cell lines. This increase was supported by mitochondrial fusion rather than mitochondrial biogenesis. Notably, as cells transitioned from a quiescent state to a proliferative state, the elongation of mitochondria occurred as quickly as 3 hours. Our results reveal that the Warburg effect, which was originally associated with dysfunctional mitochondria, does not necessitate decreased mitochondrial respiration. Rather, in many proliferating cancer cells, mitochondrial respiration is actually elevated, underscoring the importance of mitochondrial respiration during proliferation. Citation Format: Yahui Wang, Conghui Yao, Ethan Stancliffe, Ronald Fowle-Grider, Rencheng Wang, Cheng Wang, Michaela Schwaiger-Haber, Leah P. Shriver, Jason Weber, Gary J. Patti. Mitochondrial fusion is required to support higher rates of respiration in proliferating cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3773.